Alginate Microsphere Encapsulation of Drug-Loaded Nanoparticles: A Novel Strategy for Intraperitoneal Drug Delivery

Alginate hydrogels have been broadly investigated for use in medical applications due to their biocompatibility and the possibility to encapsulate cells, proteins, and drugs. In the treatment of peritoneal metastasis, rapid drug clearance from the peritoneal cavity is a major challenge. Aiming to delay drug absorption and reduce toxic side effects, cabazitaxel (CAB)-loaded poly(alkyl cyanoacrylate) (PACA) nanoparticles were encapsulated in alginate microspheres. The PACAlg alginate microspheres were synthesized by electrostatic droplet generation and the physicochemical properties, stability, drug release kinetics, and mesothelial cytotoxicity were analyzed before biodistribution and therapeutic efficacy were studied in mice. The 450 µm microspheres were stable at in vivo conditions for at least 21 days after intraperitoneal implantation in mice, and distributed evenly throughout the peritoneal cavity without aggregation or adhesion. The nanoparticles were stably retained in the alginate microspheres, and nanoparticle toxicity to mesothelial cells was reduced, while the therapeutic efficacy of free CAB was maintained or improved in vivo. Altogether, this work presents the alginate encapsulation of drug-loaded nanoparticles as a promising novel strategy for the treatment of peritoneal metastasis that can improve the therapeutic ratio between toxicity and therapeutic efficacy.     

Mycobacterium avium subsp. paratuberculosis enters the small intestinal mucosa of goat kids in areas with and without Peyer's patches as demonstrated with the everted sleeve method

The main lesions of paratuberculosis in ruminants are in the small intestine. Previous studies have shown that the bacterium enters the small intestine through M cells found in the follicle-associated epithelium lining the domes of the Peyer's patches. The everted sleeve method, devised for the in vitro study of intestinal absorption, was used in this study to investigate the uptake of Mycobacterium avium subsp. paratuberculosis in goat intestine. Everted small intestinal sleeves of goat kids, prepared from areas with and without Peyer's patches, were incubated for 60 min in 3H-labeled bacterial solution. The results of this study imply that the bacteria can enter the intestinal mucosa of the jejunum, both in areas with and without Peyer's patches. These findings indicate, therefore, that M. avium subsp. paratuberculosis bacteria not only enter through M cells but also through enterocytes.     

Deposition of gold mining tailings in tropical soils: metal pollution and toxicity to earthworms

Journal of Soils and Sediments - This study consists of the evaluation of metals acute toxicity levels taking into consideration a hypothetic scenario of dam breaking and land deposition of two...     

Larval development in European hake (Merluccius merluccius L.) reared in a semi-intensive culture system

Eggs of European hake (Merluccius merluccius L.) were stripped from fish caught at sea. Larvae were kept under semi‐intensive conditions at around 12°C. In addition, eggs were incubated in single wells at 9.2, 12.7 and 14.5°C, where hatching, development and survival were closely examined. During the larval stage, a total of 299 larvae were sampled to follow development and growth. In addition a small number of juveniles were sampled. Larvae hatched approximately 4 days after fertilization, and were 2.9 mm in total length (TL). At 6‐day post hatching (dph), the larvae were 4.1 mm (TL), the jaw apparatus was developed, and the larvae had started to feed. Most of the growth during the early larval period is restricted to the head, and there is almost no increase in length for the first 3–4 weeks post hatching. Teeth and pelvic fins appear at 25 dph. Development of unpaired fins at approximately 30 dph marks the start of the larval–juvenile transition. Weaning to formulated feed was accomplished 50 dph, when external morphology was similar to that of adult hake.     

Effect of hydrogen peroxide as treatment for amoebic gill disease in Atlantic salmon (Salmo salar L.) in different temperatures

Amoebic gill disease (AGD) is a pathogenic disease in salmonids caused by Neoparamoeba perurans. Treatment of AGD infection has been through freshwater bathing of the fish. However, as the availability of fresh water is often limited, hydrogen peroxide has been introduced as an alternative treatment. This study investigated the effect of hydrogen peroxide as treatment for AGD‐infected salmon (Salmo salar L.,) at different seawater temperatures and hydrogen peroxide dosages. In total, 600 fish were challenged with N. perurans and the severity of the AGD infection was measured using a gill score scale. After challenge and disease development, the fish were distributed into 12 tanks. The treatment was performed at different seawater temperatures (8°C, 12°C, 17°C) using different hydrogen peroxide doses. Each temperature included an untreated control group. Linear models were used to analyse gill score. A significant effect of treatment was found (?0.68 ± 0.05) regardless of dose and temperature, suggesting that hydrogen peroxide was effective in treating AGD. When the model included dose, a negative linear relationship between dose and gill score was found. The study proved that treatment of AGD with hydrogen peroxide was successful, as gills partially recovered following treatment and further disease development was delayed.     

ICP Waters — an International Programme for Surface Water Monitoring

The International Cooperative Programme on Assessment and Monitoring of Acidification of Rivers and Lakes (ICP Waters) was established in July 1985 under the United Nations Economic Commission for Europe (UN/ECE) Executive Body of the Convention on Long-Range Transboundary Air Pollution (LRTAP). The Programme Centre is at the Norwegian Institute for Water Research, Oslo. The main aim of the Programme is to assess, on a regional basis, the degree and geographical extent of acidification of surface waters. 23 countries in Europe and North America participate on a regular basis. The major findings in the programme cover (1) regional trends in water chemistry related to changes in S- and N-deposition, (2) dose/response relationships particularly between biology (invertebrates) and water chemistry (acidification status), (3) effects of acidification on aquatic fauna, (4) implications for the assessment of critical loads, and (5) nitrogen leaching. Both chemical and biological intercalibrations and intercomparisons are important parts of the programme activities.     

Genetic variation in Puccinia graminis collected from oats, rye, and barberry

Puccinia graminis, the causal agent of stem rust, was collected from its alternate host barberry (Berberis spp.) and two different uredinial hosts, oats (Avena sativa) and rye (Secale cereale). The samples were analyzed using 11 polymorphic simple sequence repeat (SSR) markers. There were large differences between fungal populations on oats (P. graminis f. sp. avenae) and rye (P. graminis f. sp. secalis), and the genetic variation within the different formae speciales was also high. It was possible to distinguish between the two formae speciales on barberry. Additional genotypic groups not present in the field samples from oats and rye were also identified on barberry. Our results confirm the importance of barberry in maintaining the populations of P. graminis in Sweden and the importance of the sexual stage for the survival of the pathogen.     

A novel IS element, ISMpa1, in Mycobacterium avium subsp. paratuberculosis

A novel insertion element belonging to the IS110 family was identified in Mycobacterium avium subsp. paratuberculosis. The IS element, ISMpa1, is 1500 bp and has one ORF encoding a putative transposase. Three copies of ISMpa1 were identified in the M. avium subsp. paratuberculosis genome. The element had inserted into the 3' end of the highly conserved mycobacterial genes prrB and a homologue of M. tuberculosis Rv1593c, and between a putative cytochrome p450 oxygenase and a putative hydrolase. The IS element was present in all (n = 11) M. avium subsp. paratuberculosis strains but not detected in most other mycobacterial species examined, including 10 M. avium subsp. avium isolates of human, avian and porcine origin. However two porcine isolates of M. avium subsp. avium and the reference strain IWGMT49 did harbour ISMpa1. These three strains belong to a previously described subgroup of M. avium subsp. avium based on IS1245 restriction fragment length polymorphism (RFLP) pattern and serovars. All of the M. avium subsp. paratuberculosis strains examined had an identical RFLP pattern when probed with sequences corresponding to the 5' end of ISMpa1, whereas a different pattern was seen in the positive M. avium subsp. avium strains. This novel IS element might be a useful tool in strain classification of M. avium subsp. avium and also for the identification of M. avium subsp. paratuberculosis when used in combination with IS900.     

Natural and experimental Salmonella Typhimurium infections in foxes (Vulpes vulpes)

The red fox (Vulpes vulpes) can be considered as a relevant indicator species for Salmonella in the local environment and Salmonella faecal carriage was investigated in 215 red foxes in Norway shot during the winters 2002/2003 and 2003/2004. Fourteen (6.5%) of the foxes carried Salmonella. Four isolates were determined as serovars Kottbus (n=2) and Hessarek (n=2) of Salmonella enterica subspecies enterica, and one as S. enterica subspecies IIIb:61:k:1,5,(7). The remaining nine isolates were S. enterica subspecies enterica serovar Typhimurium 4,12:i:1,2 and all displayed the same pulsed-field gel electrophoresis (PFGE) profile designated A2. This serovar regularly causes disease outbreaks amongst small passerine birds during winter and most of these outbreaks are associated with the PFGE profile A2. The results strongly indicated that the Salmonella Typhimurium infections in red foxes were primarily acquired through ingestion of infected small passerines. To investigate the capability of the A2 strain to establish a true intestinal infection in the fox an inoculation experiment with an A2 isolate from small passerines was carried out in farmed silver foxes (V. vulpes). The experiment also included one strain with an uncommonly occurring profile (X201) from small passerines. To highlight possible differences in capability of the two inoculation strains to pass the acid gastric juice in the fox, in vitro studies of their acid tolerance was carried out. Also their catalase activity and biofilm production were studied. All three foxes inoculated with the A2 strain developed sub-clinical intestinal infection of 2 weeks duration, whereas none of the three foxes inoculated with the X201 strain shed this bacterium. The X201 strain displayed a much lower capability, than the A2 strain, to survive at pH 3 in vitro. The low acid tolerance probably made it difficult for the X201 strain to pass the stomach and establish an intestinal infection in the experimental foxes. Reduced catalase activity and biofilm production were found for the X201 strain, indicating that the low acid tolerance was caused by a defect in the stationary-phase stress response system.